Context: Bone giant cell tumors (GCTs) are among the most common benign bone tumors and affect mostly young patients. They represent a rare etiology of head and neck cancer. Objective: We report the case of a 38-yr-old male with a GCT of the thyroid cartilage, initially treated as a thyroid cancer. Case Illustration: The patient had incomplete initial surgery, and a substantial tumor residue was observed at postoperative morphological evaluation. Given the potential risks associated with complete definitive surgery and recent data supporting the use of the receptor activator of nuclear factor κB ligand inhibitor, we proposed treatment with denosumab. Three months after initiating denosumab, computed tomography scan imaging showed a significant modification of the lesion with several calcifications. The patient underwent partial laryngectomy, and examination of the surgical specimen revealed a complete histological response. Results: A review of the literature was conducted to identify previous studies pertaining to GCTs, focusing on reports related to their management. Conclusion: Denosumab emerges as a new treatment for patients with GCTs. Additional clinical trial data are needed to establish the real efficacy and long-term safety of this treatment for the management of GCT.